Behavioural phenotyping reveals anxiety-like features of SV2A deficient mice

Behav Brain Res. 2009 Mar 17;198(2):329-33. doi: 10.1016/j.bbr.2008.11.005. Epub 2008 Nov 11.

Abstract

Synaptic vesicle protein 2A (SV2A) is involved in neurotransmitter release and has been identified as the binding site for levetiracetam (Keppra), a novel antiepileptic drug. Homozygous SV2A (-/-) mice are not viable beyond a few weeks. In contrast, heterozygous SV2A (+/-) mice have a normal lifespan. We performed a behavioural phenotyping on SV2A (+/-) mice in a battery of tests: gross behavioural observation, spontaneous locomotor activity, sensori-motor coordination, acute pain sensitivity, exploration in an elevated plus-maze and an assessment of learning abilities in an inhibitory avoidance procedure. SV2A (+/-) mice were compared to age-matched, 2-month-old wild type controls. Overall, gross behaviour, spontaneous locomotor activity, sensori-motor coordination and acute pain sensitivity were comparable between wild type and SV2A (+/-) mice. When tested in a plus-maze, SV2A (+/-) mice displayed significant increased avoidance of open elevated arms whereas locomotor activity was not altered. Finally, both SV2A (+/-) and wild type mice showed comparable memory performance at the end of a multi-trial passive avoidance procedure. Interestingly, SV2A (+/-) mice exhibited increased avoidance of the lit area during the first sessions without foot shock. These results suggest an anxiety-like phenotype for SV2A (+/-) mice indicated by increased open-arm avoidance in the elevated plus-maze test as well as a shorter latency to escape from a lit area in the inhibitory avoidance procedure.

MeSH terms

  • Animals
  • Anxiety / physiopathology
  • Anxiety / psychology*
  • Avoidance Learning*
  • Behavior, Animal*
  • Electric Stimulation / adverse effects
  • Escape Reaction*
  • Exploratory Behavior
  • Genotype
  • Maze Learning
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / genetics
  • Memory
  • Mice
  • Mice, Knockout
  • Motor Activity*
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Pain / physiopathology
  • Pain / psychology
  • Pain Threshold / psychology
  • Phenotype
  • Polymerase Chain Reaction

Substances

  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Sv2a protein, mouse